Exploring the Binding Mechanism of 5-HT7 Specific Benzoxazolone alkyl Piperazinium Derivatives: A Comprehensive Analysis Using Spectroscopic and Computational Approaches.

Recently, the 5-HT7 receptor has achieved greater attention in research fraternity due to the involvement of neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in several neurological disorders. Targeting this neuroreceptor, we have synthesized six compounds named as butyl-benzoxazolone substituted piperazinium derivatives (BBOP) derivatives, abbreviated as L1-L6. These compounds have been evaluated for their binding interaction with BSA through photophysical and in-silico approaches. The UV absorption of these compounds with BSA at λmax = 280 nm, showed an optical density (O.D.) in the range of 0.5-0.9, i.e., 21%-53% (L1max = 1.4, L5min = 0.7385) at varied concentrations (17 µM-114 µM). For fluorescence studies, the Ksv value varied inversely with temperature, which confirmed the static mechanism of quenching with L1 showing maximum quenching. The parameters (ΔH, ΔS) obtained from the thermodynamic study for interaction between BSA and L1-L6 were correlated with in-silico (molecular docking) data. The in-silico docking study showed hydrophobic and the Van der Waals forces were the most significant forces. Amino acid residues ARG 217 & TRP 213 (Sudlow Site I) and LYS 116 & GLU 125 (Sudlow Site II) of BSA were primarily involved in H-bonding.Furthermore, the catalytic activity of BSA for hydrolyzingdifferent chemical entities have monitored in the presence of L1-L6 through esterase-like assay with p-NPA as a substrate, to get more insight about the interaction with catalytic residues (LYS 414, LYS 413, and TYR 411) in BSA at site II. These findings showed the potential of these 5-HT7 markers as promising ligands with appropriate drug likeliness characteristics.

Biological Evaluation and Binding Mechanism of 5-HT7 Specific Arylpiperazinyl-Alkyl Benzothiazolone: Radiobiology and Photo-physical Studies.

Diversely substituted methoxy derivatives of arylpiperazinyl-alkyl benzothiazolone has been evaluated as specific probe for 5HT7. To determine the best methoxy derivative for 5HT7 receptor affinity, we synthesised a number of 2-benzothiazolone arylalkyl piperazine derivatives. In-vitro/vivo studies with C-2 substituted [11C]ABT showed 5HT7 specific binding. The radiochemical purity of [11C]ABT was found to be more than 99% with radiochemical stability persistence for more than 1.5 hr at 25 °C. The interaction of BSA and ABT has been analysed by photophysical studies for better understanding of properties such as adsortion, distribution, metabolism and elemination (ADME). The interaction between ABT and BSA was analyzed by using the UV-vis and fluorescence spectra. UV-vis spectra analyzed the changes in primary structure of BSA on its interaction with ABT. ABT showed quenched fluorescence emission intensity of tryptophan residues in BSA via static quenching mechanism. This study might help to understand how ABT binds to serum protein or subsequently to know the ADME of this drug candidate.

Comparison of NEWS2 and PSI as mortality predictors in patients with community acquired pneumonia.

In the West, National Early Warning Score 2 (NEWS2) is commonly applied to predict the severity of illness using only bedside variables unlike the extensive Pneumonia Severity Index (PSI). The objective of this study was to compare these scores as mortality predictors in patients admitted with community acquired pneumonia (CAP). This cross-sectional study was conducted in Jinnah Postgraduate Medical Centre, Karachi, Pakistan, for six months in 2020 on 116 patients presenting with CAP. Cases of aspiration pneumonia, hospital acquired pneumonia, pulmonary tuberculosis, pulmonary embolism, and pulmonary oedema were excluded. In-hospital mortality was taken as the outcome of this study. The mean age of the participants was 46.9±20.5 years. The in-hospital mortalities were 45(38.8%). NEWS2 was 97.8% sensitive but only 15.5% specific in predicting the outcome, whereas PSI was less sensitive (68.9%) but more specific (50.7%), which showed that in comparison with PSI, NEWS2 is a more sensitive mortality predicting score among hospitalised CAP patients.

Crystal Phase Refinement and Optical Features of Highly Efficient Green Light Radiating Ca9Y(VO4)7: Er3+ Nanophosphors for Emerging Solid-state Lighting Applications.

Ca9Y(VO4)7 phosphor activated with Er3+ ions have been developed by the urea-aided solution combustion technique. XRD profiles assisted with Rietveld refinement executed over-developed Er3+-activated Ca9Y(VO4)7 powder, revealed a trigonal phase with the R3c space group. The electron microscope techniques namely TEM and SEM characterize the size and surface-linked qualities of the developed nanopowder, respectively. The uniform distribution of various elements in the nanocrystalline sample is authenticated by an energy-dispersive spectroscopy (EDS) system. The Eg (band gap) value of 3.64 eV for Ca9Y0.9Er0.1(VO4)7 and 3.74 eV for Ca9Y(VO4)7 has been estimated. Upon 382 nm excitation, Er3+: Ca9Y(VO4)7 phosphor gives rise to the bright green emission owing to the 4S3/2 → 4I15/2 transition. The concentration quenching after 10 mol% composition of trivalent erbium ions is attributed to dipole-dipole interlinkages in accordance with Dexter's theory. The radiative lifetime (1.1083 ms), non-radiative rates (0.2079 ms- 1), quantum efficiency (79%), along with colorimetric parameters i.e. CIE x (= 0.2577), y (= 0.4566), and CCT quantities offer Ca9Y0.9Er0.1(VO4)7 as a proficient green radiating nanomaterial for RGB phosphors in solid-state applications.

[99mTc-BBPA]: A possible SPECT agent to understand the role of 18-kDa translocator protein (PBR/TSPO) during neuro-glial interaction.

The translocator protein (TSPO, 18 kDa) is one of the most promising biomarker to understand the role of neuroinflammation in human as well as in different animal species. Here we report a new TSPO-selective ligand 2-(5-(2-(bis(pyridin-2-yl methyl)amino)acetamido)-2-oxobenzo[d] oxazol-3(2H)-yl)-N-methyl-N-phenylacetamide, BBPA, which is supposed to be a potential probe to understand the role of TSPO in neuro-glial interaction through SPECT modality.

Benzoxazolone-arylpiperazinyl scaffold-based PET ligand for 5-HT7 : Synthesis and biological evaluation.

Efforts are underway to improve the diagnosis and treatment for neurological disorders like depression, anxiety, epilepsy, and schizophrenia. The G-protein-coupled receptors (GPCRs) 5-HT7   receptor, the most recently identified member of 5-HT receptor family dysregulation has an association with various central nervous system (CNS) disorders and its ligands have an edge as potential therapeutics. Here, we report the synthesis, characterization, and biological evaluation of diversely substituted methoxy derivatives of 2-benzoxazolone arylpiperazine for targeting 5-HT7  receptors. Out of all derivatives, only C-2 substituted derivative, 3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzoxazol-2(3H)-one/ABO demonstrate a high affinity for human 5-HT7 receptors. [11 C]ABO was obtained by O-methylation of desmethyl-precursor using [11 C]CH3 OTf in the presence of NaOH giving a high radiochemical yield of 25 ± 12% (decay-corrected, n = 7) with stability up to 1.5 h postradiolabeling. In vitro autoradiography displays binding of [11 C]ABO in accordance with 5-HT7 distribution with a decrease of approximately 80% and 40% activity in the hippocampus and cerebellum brain region when administered with 10 µM cold ligand. Prefatory positron emission tomography scan results in Sprague-Dawley (SD) rat brain revealed fast and high radioactivity build-up in 5-HT7 receptor-rich regions, namely, the hippocampus (2.75 ± 0.16 SUV) and the cerebral cortex (2.27 ± 0.02 SUV) establishing selective targeting of [11 C]ABO. In summary, these pieces of data designate [11 C]ABO as a promising 5-HT7  receptor ligand that can have possible roles in clinics after its further optimization on different animal models.

Synthesis and evaluation of technetium-99m labelled 1-(2-methoxyphenyl)piperazine derivative for single photon emission computed tomography imaging for targeting 5-HT1A.

Quantitative changes in expression level of 5HT1A are somewhere related to common neurological disorders such as anxiety, major depression and schizophrenia. We have designed EDTA conjugated SPECT imaging probe for localization of 5HT1A receptor in brain. For designing SPECT probe we have employed the concept of bivalent approach and a homodimeric system with desirable pharmacokinetics of 5HT1A imaging. 99mTc-EDHT was also evaluated for its stability through serum stability assay and glutathione challenge experiment. Biodistribution study showed the highest accumulation of radioactivity in kidney which depicted the renal mode of excretion from the body. However in brain the uptake of 1.21% ID per gram was observed in initial 5 min of drug administration. On blocking the receptor this percent get decreased to 0.97% ID per gram. The regional distribution in brain was also performed which showed the accumulation of drug in cerebellum, cortex and hippocampus part, which are already known for 5HT1A expression. Dynamic study in rabbit is also in support of results derived from biodistribution and blood kinetics experiment. These finding suggest that 99mTc-EDHT holds promising place for further optimization before nuclear medicine applications in different animal species.

Design and development of an optical reflective notch filter using the ion assisted deposition technique with stepwise modulated thickness for avionics applications.

This paper presents research work about the design and fabrication of a 44-layer optical reflective notch filter. The performance of the fabricated notch filter was studied at normal (0°) and oblique (45°) incidence angle. In addition, the paper also discusses a three-layer broadband antireflective coating on both sides of the multilayer stack to suppress the ripples in the passband region. The thickness-modulated reflective stack of the filter was designed by using the materials Al2O3 (1.63) and SiO2 (1.46). Optimization of the multilayer stack was carried out by using the damped least-squares algorithm. The theoretical and experimental results from the ion-assisted e-beam deposited samples for single notch reflective filters are presented. Good agreement in the design and experimental results was observed when the deposition process was controlled by time of evaporation. Further, the filter was characterized for the optical properties by using a UV-VIS-NIR spectrophotometer, surface morphology and protective properties using field emission scanning electron microscopy, a coherence correlation interferometer, and water contact angle.

Ouabain potentiates the antimicrobial activity of aminoglycosides against Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a notorious pathogen which often causes nosocomial and community attained infections. These infections steadily increased after evolving the resistance due to indecorous practice of antibiotics and now become a serious health issue. Ouabain is a Na+/K+-ATPase inhibitor that leads to increase the heart contraction in patients with congestive heart failure. METHODS: In the present study, in vitro antimicrobial effect of ouabain together with aminoglycosides was determined against clinical and non-clinical S. aureus strains. Using checkerboard, Gentamycin uptake and biofilm assays, we analysed he interactions of ouabain with aminoglycosides. RESULTS: Ouabain induced the staphylocidal potency of aminoglycosides by remarkably reducing the MIC of gentamycin (GEN) by 16 (0.25 µg/mL), 8 folds (0.5 µg/mL) amikacin (AMK); and 16 folds (1.0 µg/mL) with kanamycin (KAN), compared to their individual doses. OBN severely reduced cell viability within 60 min with GEN (1 µg/mL), KAN (2 µg/mL) and 90 min with AMK (1 µg/mL). This bactericidal effect was enhanced due to GEN uptake potentiated by 66% which led to increase the cell permeability as revealed by leakage of bacterial ATP and nitrocefin assay. The biofilm adherence disrupted by 80 and 50% at 5 mg/mL and 1.5 mg/mL OBN and 50 and 90% biofilm formation was inhibited at 5 mg/mL (MBIC50) and 10 mg/mL (MBIC90), respectively. Moreover, OBN with GEN further induced biofilm inhibition by 67 ± 5% at pH 7.0. CONCLUSIONS: Taken together, we established that OBN synergizes the antimicrobial activity of aminoglycosides that induces cell killing due to intracellular accumulation of GEN by disturbing cell homeostasis. It may be proven an effective approach for the treatment of staphylococcal infections.

Association of plasma osteopontin with diabetic retinopathy in Asians with type 2 diabetes.

Purpose: Osteopontin (OPN) is a proinflammatory cytokine with diverse functions. Increased levels of OPN in vitreous fluid have been reported in patients with diabetic retinopathy (DR); however, studies on circulating OPN levels in DR are limited. We aim to examine the association of plasma OPN levels with the presence and severity of DR in a multiethnic cohort with type 2 diabetes mellitus (type 2 diabetes) in Singapore. Methods: Plasma levels of OPN were measured using enzyme-linked immunosorbent assay. Digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR). Gradable fundus photographs and OPN measurements for 443 patients were used for analysis. A logistic regression model was used to evaluate the association of OPN with DR. Results: DR was diagnosed in 174 (39.3%) patients, including 132 (75.9%) with NPDR and 42 (24.1%) with PDR. The median of OPN was higher in the patients with DR (64.7 [49.7-89.5] ng/ml) than in the patients without DR (51.7 [38.9-66.9] ng/ml; p<0.001). After adjustment for clinical and biochemical factors, a 1-unit increase in nature logarithm (ln)-transformed OPN was associated with the presence of DR (2.770 [1.599-3.800], p<0.001). The area under the curve (AUC) increased statistically significantly after the addition of OPN (0.805[0.763-0.846] versus 0.825 [0.785-0.865], p=0.011). In the severity analyses, the median of OPN was statistically significantly higher in the patients with PDR (76.8 [55.0-103.6] ng/ml) than in the patients with NPDR (61.7 [47.7-87.3] ng/ml; p=0.017). After adjustment, the 1-unit increase in lnOPN remained associated with NPDR (2.673 [1.519-4.704], p=0.001) and PDR (3.389 [1.254-9.226], p=0.017), respectively (p-trend=0.001). Conclusions: Plasma OPN levels were associated with the presence and severity of DR in patients with type 2 diabetes, suggesting OPN may be useful as a potential biomarker for DR.

Impact of Incidence and Progression of Diabetic Retinopathy on Vision-Specific Functioning.

PURPOSE: To investigate the independent impact of the incidence and progression of diabetic retinopathy (DR) on visual functioning (VF). DESIGN: Population-based cohort study. PARTICIPANTS: A total of 518 participants aged 40 to 80 years (baseline visit 2007-2009 and second visit 6 years later, 2013-2015), with diabetes, clinical data, and VF information at both visits. MAIN OUTCOME MEASURES: VF-7 scores, converted to interval-level person measures (in logits) using Rasch analysis. METHODS: Incident DR was defined using the Modified Airlie House classification as "none or minimal" DR at baseline and at least mild nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe nonproliferative DR, proliferative DR, and/or clinically significant macular edema) as no VTDR at baseline, and present at follow-up; and DR progression as at least a 1-step worsening in DR at follow-up from mild or worse status at baseline. The longitudinal associations between incident DR, VTDR, and DR progression, as well as change in composite and individual item scores of VF, were assessed using multivariable linear regression models. RESULTS: Of the 518 participants (mean age ± standard deviation [SD] 59.8±9.0 years; 47.7% female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and DR progression, respectively, at follow-up. In models adjusting for traditional confounders, persons with incident DR and VTDR had a 13.7% (ß = -0.60; 95% confidence interval [CI], -0.96 to -0.24; P = 0.001) and 23% (ß = -1.00; 95% CI, -1.61 to -0.38; P = 0.001) reduction in mean VF scores at follow-up. Furthermore, individuals with incident DR had similar independent reductions in scores for 7 individual items of the VF-7, whereas those with incident VTDR had the largest reductions for activities like cooking (31%; P = 0.003), reading the newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow-up. Progression of DR was not independently associated with change in overall VF (ß = -0.18; 95% CI, -1.00, 0.64; P = 0.660). CONCLUSIONS: Incident DR, particularly vision-threatening stages, has a substantial negative impact on people's overall vision-dependent functioning and specific activities such as cooking, seeing street signs, and reading the newspaper. Our findings reinforce the need for strategies to prevent or delay the development of DR.

Retinal vascular geometry and 6 year incidence and progression of diabetic retinopathy.

AIMS/HYPOTHESIS: We aimed to examine prospectively the association between a range of retinal vascular geometric variables measured from retinal photographs and the 6 year incidence and progression of diabetic retinopathy. METHODS: We conducted a prospective, population-based cohort study of Asian Malay individuals aged 40-80 years at baseline (n = 3280) who returned for a 6 year follow-up. Retinal vascular geometric variables (tortuosity, branching, fractal dimension, calibre) were measured from baseline retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). Diabetic retinopathy was graded from baseline and follow-up photographs using the modified Airlie House classification system. Incidence of diabetic retinopathy was defined as a severity of ≥15 at follow-up among those without diabetic retinopathy at baseline. Incidence of referable diabetic retinopathy was defined as moderate or severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or diabetic macular oedema at follow-up in participants who had had no or mild non-proliferative diabetic retinopathy at baseline. Progression of diabetic retinopathy was defined as an increase in severity of ≥2 steps at follow-up. Log-binomial models with an expectation-maximisation algorithm were used to estimate RR adjusting for age, sex, diabetes duration, HbA1c level, BP, BMI, estimated GFR and total and HDL-cholesterol at baseline. RESULTS: A total of 427 individuals with diabetes participated in the baseline and 6 year follow-up examinations. Of these, 19.2%, 7.57% and 19.2% developed incidence of diabetic retinopathy, incidence of referable diabetic retinopathy and diabetic retinopathy progression, respectively. After multivariate adjustment, greater arteriolar simple tortuosity (mean RR [95% CI], 1.34 [1.04, 1.74]), larger venular branching angle (RR 1.26 [1.00, 1.59]) and larger venular branching coefficient (RR 1.26 [1.03, 1.56]) were associated with incidence of diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.82 [1.32, 2.52]), larger venular branching coefficient (RR 1.46 [1.03, 2.07]), higher arteriolar fractal dimension (RR 1.59 [1.08, 2.36]) and larger arteriolar calibre (RR 1.83 [1.15, 2.90]) were associated with incidence of referable diabetic retinopathy. Greater arteriolar simple tortuosity (RR 1.34 [1.12, 1.61]) was associated with diabetic retinopathy progression. Addition of retinal vascular variables improved discrimination (C-statistic 0.796 vs 0.733, p = 0.031) and overall reclassification (net reclassification improvement 18.8%, p = 0.025) of any diabetic retinopathy risk beyond established risk factors. CONCLUSIONS/INTERPRETATION: Retinal vascular geometry measured from fundus photographs predicted the incidence and progression of diabetic retinopathy in adults with diabetes, beyond established risk factors.

Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential anticancer agent: Synthesis and evaluation.

With the rising incidences of cancer cases, the quest for new metal based anticancer drugs has led to extensive research in cancer biology. Zinc complexes of amino acid residue side chains are well recognized for hydrolysis of phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II) complex of cyclen substituted with two l-tryptophan units, Zn(II)-Cyclen-(Trp)2 has been synthesized and evaluated for antiproliferative activity. Zn(II)-Cyclen-(Trp)2 was synthesized in ∼70% yield and its DNA binding potential was evaluated through QM/MM study which suggested good binding (G=-9.426) with B-DNA. The decrease in intensity of the positive and negative bands of CT-DNA at 278nm and 240nm, respectively demonstrated an effective unwinding of the DNA helix with loss of helicity. The complex was identified as an antiproliferative agent against U-87MG cells with 5 fold increase in apoptosis with respect to control (2h post incubation, IC50 25µM). Electrophoresis and comet assay studies exhibited an increase in DNA breakage after treatment with complex while caspase-3/ß-actin cleavage established a caspase-3 dependent apoptosis pathway in U-87 MG cells after triggering DNA damage. In vivo tumor specificity of the developed ligand was validated after radiocomplexation with 99mTc (>98% radiochemical yield and specific activity of 2.56GBq/µmol). Avid tumor/muscle ratio of >6 was depicted in biodistribution and SPECT imaging studies in U-87 MG xenograft model nude mice.

Singapore Indian Eye Study-2: methodology and impact of migration on systemic and eye outcomes.

IMPORTANCE: Asian Indians are the fastest growing migration groups in the world. Studies evaluating the impact of migration on disease outcomes in this population are rare. BACKGROUND: We describe the methodology of the Singapore Indian Eye Study-2 (SINDI-2) aimed to evaluate the impact of migration status on diabetic retinopathy and other major age-related eye diseases in Asian Indians living in an urban environment. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 2200 adults had participated in baseline SINDI (2007-2009, mean age [range] = 57.8 [42.7-84.1] years) and SINDI-2 (2013-2015, 56.5 [48.4-90.2] years). METHODS: Participants were classified as 'first generation' if they were Indian residents born outside of Singapore and as 'second-generation' immigrants (59.7% in SINDI vs. 63.6% in SINDI-2) if they were born in Singapore. MAIN OUTCOME MEASURES: Response rate, participant characteristics and prevalence of systemic diseases were stratified by migration status. RESULTS: Of the 2914 eligible SINDI participants invited to participate, 2200 participated in SINDI-2 (response rate of 75.2%). In both SINDI and SINDI-2, compared with first-generation immigrants, second-generation immigrants were younger, less likely to have income <1000 SGD, had lower levels of pulse pressure, higher levels of high-density lipoprotein cholesterol, had lower prevalence of hypertension and chronic kidney disease and had higher prevalence of current smoking and obesity (all P < 0.05). CONCLUSIONS AND RELEVANCE: In both SINDI and SINDI-2, second-generation immigrants had lower prevalence of cardiovascular risk factors except smoking and obesity compared with first-generation immigrants. The final report will confirm if these differences between generations are evident with regard to eye diseases.

Esophageal Melanocytosis - An Unusual Melanocytic Entity.

Esophageal melanocytosis is a rare benign condition characterized by melanocytic proliferation in esophageal squamous epithelium and melanin deposition in the mucosa. Because of its uncommon nature, pathologists and gastroenterologists lack experience with this entity. We present a case of esophageal melanocytosis in a 66 years old male patient who presented with atypical chest pain and dysphagia. Endoscopic guided biopsy was done, provisional diagnosis of esophageal melanocytosis was made. Bleaching and immunohistochemistry confirmed the diagnosis.

Investigations on preferential Pu(IV) extraction over U(VI) by N,N-dihexyloctanamide versus tri-n-butyl phosphate: evidence through small angle neutron scattering and DFT studies.

Straight chain amide N,N-dihexyloctanamide (DHOA) has been found to be a promising alternative extractant to tri-n-butyl phosphate (TBP) for the reprocessing of irradiated uranium- and thorium-based fuels. Unlike TBP, DHOA displays preferential extraction of Pu(IV) over U(VI) at higher acidities (≥3 M HNO3) and poor extraction at lower acidities. Density functional theory (DFT) based calculations have been carried out on the structures and relative binding energies of U(VI) and Pu(IV) with the extractant molecules. These calculations suggest that the differential hardness of the two extractants is responsible for the preferential binding/complexation of TBP to uranyl, whereas the softer DHOA and the bulky nature of the extractant lead to stronger binding/complexation of DHOA to Pu(IV). In conjunction with quantum chemical calculations, small angle neutron scattering (SANS) measurements have also been performed for understanding the stoichiometry of the complex formed that leads to relatively lower extraction of Th(IV) (a model for Pu(IV)) as compared to U(VI) using DHOA and TBP as the extractants. The combined experimental and theoretical studies helped us to understand the superior complexation/extraction behavior of Pu(IV) over U(VI) with DHOA.

Morphometric Analysis of Glenopolar Angle of the Scapula in Indian Population.

BACKGROUND: The glenopolar angle (GPA), usually ranges from 30° to 45°. GPA measures the tilt of the plane of the glenoid cavity in relation to the axis of the body of the scapula passing from the superior pole of the glenoid cavity to the inferior angle of the scapula. It is essential to assess the results of surgeries for dislocated shoulders. Worse long-term outcomes can arise from glenoid misalignment in scapular neck fractures. When evaluating prognosis and planning therapy for shoulder injuries including scapular fractures, GPA assessment is essential. Still, there is a dearth of data on the normal range of GPA and its contributing elements, which calls for more study. The purpose of this study is to determine typical GPA values by utilizing radiographs and a sizable sample of scapular bone specimens. METHODS: In this study, the GPA was assessed in 50 chest radiographs of anteroposterior (AP) view and Neer's view of individuals as well as 100 dried scapulae of any gender. The mean GPA obtained using the various methods was then statistically compared. FINDINGS: All scapulae had an average GPA of 42.6°. Twenty-nine scapulae had GPA observations higher than 45°, with an average of 47.2°. Twenty-seven scapulae had GPA measurements below 40°, averaging 37.3°. Right-sided 62 scapulae with an average GPA of 43.1° were present. Thirty-eight of left-side scapulae had a GPA of 41.7° on average. It was determined that the 1.6° mean difference in GPA between the two groups was not statistically significant. The Kolmogorov-Smirnov test verified that the GPA data had a normal distribution. The homogeneity of variances across various measuring techniques was confirmed using Levene's test. The average GPA measured using the dry scapula approach was 42.6°, the average GPA measured using the AP view was 39.8°, and the average GPA measured using the Neer I view was 42.3°. The GPA means from these three approaches differed considerably (p=0.0014) according to a one-way Analysis of Variance (ANOVA). Fisher's least significant difference post hoc testing showed that the scapular bone specimens and the Neer I view revealed significantly higher GPA values than AP shoulder radiographs. The GPA values obtained from the osteological group and the Neer I perspective had a mean difference of 0.21°, which was practically identical and suggested that there was no statistically significant difference between these approaches. IN SUMMARY: In order to diagnose and treat a variety of shoulder joint diseases, this study estimates the normal values of scapular GPA. Furthermore, it offers support for improved implant design in the context of Indian shoulder joint replacement and repair. Using every measurement technique, the GPA values on the right and left sides did not differ significantly. GPA results from various measuring methods varied significantly, which emphasizes the significance of methodological consistency in clinical and research settings.

Identification of different extracts and phytoconstituents of Callistemon viminalis Cheel for their anti-anxiety effects based on pharmacognostic, toxicological, and pharmacological strategies.

Background: Psychiatric disorders like depression and anxiety are global challenges, exacerbated by the limitations of synthetic medications, including addiction and toxic side effects. Methods: This study meticulously investigated the pharmacognostic, phytochemical, toxicological, and pharmacological properties of Callistemon viminalis Cheel. Toxicological assessments, including hemocompatibility assays, LD50 studies, FOB analysis, biochemical parameters, and structural integrity of vital organs, were conducted on aqueous, methanolic, chloroform, and petroleum ether extracts of leaves and stems. Phytochemical profiling via qualitative tests and GC-MS screened extracts for molecular docking against key receptors. Categorically screened extracts were evaluated for therapeutic potential against LPS-induced anxiety in mice. Results: Toxicological evaluations on experimental animals demonstrated the safety of various extracts, evidenced by no in vitro and in vivo toxicity. GC-MS identified numerous phytochemicals that passed "Lipinski's Rule of Five." These compounds were screened for molecular docking, revealing significant binding affinities with CB1, SERT, α2A-AR, and GABAß2 receptors, suggesting potential therapeutic effects against anxiety. The phytoconstituents with the highest docking scores, particularly in aqueous and methanolic extracts, were further validated for their therapeutic efficacy. Preliminary analysis based on the EPM test and serum cortisol levels confirmed these extracts' superior therapeutic effectiveness. Conclusion: In conclusion, aqueous and methanolic extracts of Callistemon viminalis Cheel's leaf and stem showed promising potential as therapeutic interventions for anxiety disorders.

Synchronized cardioversion resolving refractory supraventricular tachycardia in a neonate: a case report with comprehensive analysis.

Introduction and importance: Neonatal supraventricular tachycardia (SVT) poses unique challenges in diagnosis and management, with refractory cases requiring synchronized cardioversion being exceptionally rare. This case report explores the presentation and management of refractory SVT in a neonate, emphasizing the significance of sharing such clinical scenarios. Case presentation: A 16-day-old neonate, born via emergency caesarean section, presented with respiratory distress, poor feeding, and vomiting. Initial diagnosis of SVT was made on the basis of electrocardiography (ECG) changes. Initial attempts with adenosine failed, leading to the recurrence of tachycardia. Despite amiodarone administration, the tachycardia persisted, prompting synchronized cardioversion. Post-cardioversion, the neonate was managed with oral medications, showing sustained improvement. Clinical discussion: This case report highlights a neonate with refractory SVT, requiring synchronized cardioversion, presenting a rare and challenging scenario. The report addresses diagnostic challenges, treatment approaches, and potential mechanisms for refractory SVT, such as delayed presentation and resistance to adenosine. Emphasizing individualized care plans and vigilant monitoring, this report is a valuable resource for healthcare professionals, contributing to neonatal cardiology understanding and emphasizing the importance of early recognition and effective interventions. Ongoing follow-up and successful outcomes underscore the need for sustained management strategies. Conclusion: This case report sheds light on the rarity of refractory SVT in neonates, emphasizing the complexities in diagnosis and management. Successful synchronized cardioversion and subsequent oral therapy highlight the need for a multifaceted approach in neonatal SVT cases. The implications for clinical practice underscore the importance of awareness and continued research in neonatal cardiology and emergency medicine.